Campylobacter jejuni (C.jejuni) is the leading bacterial cause of food born diarrheal illness and enterocolitis worldwide in human and young animals. A total of 140 samples (100 fecal samples of calves and 40 raw milk samples of cow) were collected from Dakahlia governorate dairy farms for isolation and identification of C.jejuni by using cultural, biochemical, molecular methods and detection of the virulent cadF gene using PCR. Moreover, the isolated C.jejuni subjected for antimicrobial susceptibility test. Then, we develop an experimental infection of rabbits by inoculation with 1 × 10 9 colony-forming units (cfu) of completely identified C.jejuni. Rabbits divided into 3 groups: infected untreated (G1), infected treated with enrofloxacine (G2), control (G3) to study pathogenesis, fecal inflammatory response, histopthology, immunohistochemistry and ultrastructural changes post inoculation in the three groups. Results revealed that, from 140 fecal and raw milk samples only 41 isolates were bacteriologically and biochemically identified as Campylobacter spp. Seven isolated strains were positively amplified for mapA gene specific to C.jejuni and carried the cadF virulence gene. C.jejuni isolates were resistant to amoxicillin and ampicillin and highly susceptible to norfloxacine and erythromycin. After oral infection with C. jejuni 90% of rabbits developed diarrhea with highly fecal inflammatory responses in G1, but mild in G2 (treated) and negative in G3 (control). Pronounced histopathologic changes were investigated in G1 during the acute phase (days 1 to 3) restricted on distal small intestine and colon including massive destruction of villi and loss of intestinal glands. The submucosa and muscularis mucosa showed the presence of edema with congested blood vessels, while hemorrhage was seen in the muscularis propria layer. The changes were mild and involved only the villi in treated group (G2), while abscent in control (G3). These results were confirmed by immunostaining, suggesting that C.jejuni is capable of invading deep intestinal tissues down to the submucosal layer in G1 while in G2 infection, the reaction was confined mainly to the villi, and was greatly reduced in the submucosa. Electron microscope showed all stages of invasion and associating damages from postinfection, colonizationa and villus damage. Thereby, the implementation of hyagenic practices during milking and proper handling of milk during calves feeding with regular monitoring of antibiogram profile are very crucial in preventing C.jejuni infection, colonization and intestinal damage and subsequently economic loss in dairy farm.